UNIGE document Scientific Article
previous document  unige:45055  next document
add to browser collection
Title

Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice

Authors
Schäfer, Matthias
Willrodt, Ann-Helen
Kurinna, Svitlana
Link, Andrea S
Farwanah, Hany
Geusau, Alexandra
Gruber, Florian
show hidden authors show all authors [1 - 18]
Published in EMBO Molecular Medicine. 2014, vol. 6, no. 4, p. 442-57
Abstract The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/"metabolizing acquired dioxin-induced skin hamartomas" (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.
Keywords AnimalsCells, CulturedChloracne/genetics/metabolismDisease Models, AnimalEpigen/genetics/metabolismHair Follicle/metabolismHumansKeratinocytes/metabolismMiceMice, TransgenicNF-E2-Related Factor 2/genetics/metabolismSecretory Leukocyte Peptidase Inhibitor/genetics/metabolism
Identifiers
PMID: 24503019
Full text
Article (Published version) (3.4 MB) - public document Free access
Structures
Research group La recherche en biochimie dermatologique (652)
Citation
(ISO format)
SCHÄFER, Matthias et al. Activation of Nrf2 in keratinocytes causes chloracne (MADISH)-like skin disease in mice. In: EMBO Molecular Medicine, 2014, vol. 6, n° 4, p. 442-57. https://archive-ouverte.unige.ch/unige:45055

265 hits

355 downloads

Update

Deposited on : 2015-01-13

Export document
Format :
Citation style :